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Antigen trafficking

Depends on the route of entry. If it penetrates the tissues, it will end up in a draining lymph node. Those encountered in the URT or intestine are trapped by local MALT, whereas antigens in the blood provoke a reaction in the spleen. Macrophages in the liver will filter blood-borne antigens and degrade them without producing an immune response since they are not strategically placed with respect to lymphoid tissue.

Dendritic cell maturation

Receptors involved in antigen capture, including the mannose receptor and Fc receptors for both IgG and IgE, are present on dendritic cells. The expression of cell surface MHC class II, and of adhesion and costimulatory molecules, is low at this early stage of the dendritic cells’ life. However, as they differentiate into fully fledged antigen-presenting cells, they decrease their phagocytic and endocytic activity, show reduced levels of molecules involed in anitgen capture, but dramatically increase their MHC class II. Costimulatory molecules such as CD40, CD80 (B7.1) and CD86 (B7.2) are also upregulated at this stage as is the ICAM-1 adhesion molecule which is thought to contribute to both the migratory and antigen-presenting properties of these cells. Their expression of CD4 and the chemokine receptors CCR5 and CXCR4 means that they are atracted to and migrate into T cell areas and incidentally become susceptible to infection by HIV.

Lymphocyte homing

Lymphocytes are directed to specific tissues via specific homing receptors. Dendritic cells from the appropriate tissue play an important role in selectively imprinting the correct address code during their activation of naïve T cells

Lymphocyte trafficking

Antigen-reactive cells are depleted from the circulating pool of lymphocytes within 24 hours of antigen first localizing in the lymph nodes or spleen; several days later, after proliferation at the site of antigen localization, a peak of activated cells appears in the thoracic duct. When antigen reaches a lymph node in a primed animal, there is a dramatic fall in the output of cells in the efferent lymphatics (cell shutdown). This is followed by an output of activated blast cells which peaks at around 80 hours.

T cell priming

Peripheral immature dendritic cells can pick up and process antigen. As maturation proceeds, they lose their E-cadherin and produce collagenase, presumably to facilitate their crossing of the basement membrane (LCs). They then travel as ‘veiled’ cells in the lymph before settling down as IDCs in the paracortical T cell zone of the draining lymph node. There, maturation is completed, the IDC delivers the antigen with costimulatory signals for potent simulation of naïve and subsequently of activated, specific T cells, which take advantage of the large surface area to bind to the MHC-peptide complex on the IDC membrane.

TCR binding to MHC

Non-covalent interaction. Should the TCR on the T cell recognize the cognate MHC-peptide, a stable binding occurs which is largely cemented by LFA-1 on the T cell binding to ICAM-1 on the IDC. An immunological synapse is generated and contact maintained for 36-48 hours in order to fully activate the T cell.